The effects on the contralateral SI cortex of two different (non-noxious mechanical versus thermal) modes of natural skin stimulation will be studied in intact subjects, and also in subjects lacking either the spinal dorsal column or spinothalamic project pathways. Anesthetized squirrel monkeys will serve as subjects. In each subject a combination of the methods of near-infrared optical intrinsic signal (OIS) imaging and extracellular microelectrode recording will be used to obtain information about the SI neuron population and single neuron responses to the two modes of skin stimulation. In each subject recordings of the spike discharge activity evoke from single SI neurons by each model of skin stimulation. In each subject recordings of the spike discharge activity of the spike discharge activity evoked from single SI neurons by each mode of skin stimulation will be obtained from neurons located in functionally contrasting SI regions (e.g. regions in which the skin stimulus evokes increased vs. regions which undergo a decrease in activity. The microelectrode penetrations will be guided by high-resolution OIS images of the SI optical response to the same stimuli used to evoke single neuron discharge activity. In some experiments direct application of drugs to cerebral cortex or to spinal cord will be used to distinguish the contributions to the SI responses of activity in the NMDA receptor systems of cerebral cortex versus dorsal horn. The project is expected to generate novel information about the contributions of stimulus-directed cortico-cortical interactions to SI information processing and somesthesis. The findings also should bear on current theories of the CNS mechanisms of nonciception and pain